Response to Intra-Arterial and Combined Intravenous and Intra-Arterial Thrombolytic Therapy in Patients With Distal Internal Carotid Artery Occlusion * Editorial Comment

Department of Neurology, Case Western Reserve University/University Hospitals of Cleveland, Ohio 44106, USA.
Stroke (Impact Factor: 5.72). 07/2002; 33(7):1821-6. DOI: 10.1161/01.STR.0000020363.23725.67
Source: PubMed


The objective of this study was to determine the clinical features, angiographic findings, and response to treatment with thrombolytic therapy in patients with ischemic stroke caused by acute occlusion of the distal internal carotid artery.
This is a retrospective case series from a prospectively collected stroke database for patients with acute internal carotid occlusion presenting within 6 hours of stroke onset to evaluate safety, feasibility, and response to thrombolytic therapy. The University Hospital-based brain attack database was reviewed over a 5-year period. Demographics, clinical features, stroke mechanisms, severity, imaging findings, type of thrombolysis, treatment responses, mortality, and long-term outcome using modified Rankin Scale and Barthel Index were determined. The short-term outcome was assessed using the National Institutes of Health Stroke Scale (NIHSS). Acute thrombolytic therapy was administered using recombinant tissue plasminogen activator or urokinase given intra-arterially or in combination with intravenous (IV) routes.
Two hundred seven patients treated with thrombolysis between 1995 and 2000 were reviewed, and of these, 101 were studied with cerebral angiography. Eighteen patients were identified with acute ischemic stroke and ipsilateral occlusion of the distal internal carotid artery. Time to treatment was the most powerful predictor of response to thrombolytic therapy (P<0.001). The response to therapy also correlated well with the severity of the initial clinical deficit as judged by the NIHSS (P<0.001). There was no difference in recanalization rate, symptomatic hemorrhage, and NIHSS for IV/intra-arterial (IA) versus IA alone (P=NS). Complete angiographic recanalization was accomplished in 80% of those who received combined IV/IA thrombolysis and in 62% of those who received IA therapy (P=NS). Those with distal occlusions extending to the middle and anterior cerebral arteries were the least likely to respond to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 20% of the patients receiving IV/IA therapy, and in 15% of the IA only (P=NS). At 24 hours, the NIHSS dropped by 3 points in the IA group and 4 points in the IV/IA group (P=NS). Mild disability with independence was found in 77% of the survivors at 3-month follow-up. The mortality rate was 50% in this group despite thrombolysis.
Thrombolytic therapy using a combination of IV and IA routes and using the IA-only route may be effective in improving outcome for the patients suffering from occlusion of the distal internal carotid artery. Shorter intervals between onset and treatment seem to be correlated with higher rate of recanalization and improved outcome.

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    • "Thromboembolic occlusion of major cerebral arteries is usually a very serious condition and successful recanalization improves outcomes. Unfortunately, such lesions are often refractory to intravenous (IV) and/or intra-arterial (IA) thrombolysis1,15,25,28). Endovascular intervention offers good result in the treatment of acute ischemic stroke in patients presenting beyond the 4.5-hour time window, as well as in patients presenting in less than 4.5-hours who are ineligible for tissue plasminogen activator (tPA) or have failed to respond to IV tPA. "
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    ABSTRACT: Sudden major cerebral artery occlusion often resists recanalization with currently available techniques or can results in massive symptomatic intracranial hemorrhage (sICH) after thrombolytic therapy. The purpose of this study was to examine mechanical recanalization with a retrievable self-expanding stent and balloon in acute intracranial artery occlusions. Twenty-eight consecutive patients with acute intracranial artery occlusions were treated with a Solitaire retrievable stent. Balloon angioplasty was added if successful recanalization was not achieved after stent retrieval. The angiographic outcome was assessed by Thrombolysis in Cerebral Infarction (TICI) and the clinical outcomes were assessed by the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). At baseline, mean age was 69.4 years and mean initial NIHSS score was 12.5. A recanalization to TICI 2 or 3 was achieved in 24 patients (85%) after stent retrieval. Successful recanalization was achieved after additional balloon angioplasty in 4 patients. At 90-day follow-up, 24 patients (85%) had a NIHSS improvement of ≥4 and 17 patients (60%) had a good outcome (mRS ≤2). Although there was sICH, there was one death associated with the procedure. Mechanical thromboembolectomy with a retrievable stent followed by additional balloon angioplasty is a safe and effective first-line therapy for acute intracranial artery occlusions especially in case of unsuccessful recanalization after stent thrombectomy.
    Journal of Korean Neurosurgical Society 02/2013; 53(2):77-82. DOI:10.3340/jkns.2013.53.2.77 · 0.64 Impact Factor
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    • "For instance, the half life-time of urokinase is only 10–15 min in human body (Erdogan et al., 2005). Thus protein drugs may have to be administrated at a high level close to the maximum tolerated dose to the patients in order to get a therapeutical concentration in the targeted site (Zaidat et al., 2002). However, such strategy is not applicable to many proteins like the rt-PA or uPA because an increased blood drug concentration of those drugs will cause serious sideeffects such as hemorrhage (Brekenfeld et al., 2007). "
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    ABSTRACT: To find a way to modulate the effect of thrombolytic proteins by increasing their specificity, minimizing their adverse effect as well as lengthening their circulation time for the treatment of ischemic vascular disease holds great promise. In this work, urokinase-type plasminogen activator (uPA) was encapsulated into hollow nanogels which are generated by the reaction of glycol chitosan and aldehyde capped poly(ethylene glycol) (OHC-PEG-CHO) through a one-step approach of ultrasonic spray. The uPA-loaded nanogels, with size of 200-300 nm, have longer circulation time than that of the nude urokinase in vivo, besides the protein can be triggered to release in faster rate under diagnostic ultrasonic condition of 2 MHz, which significantly enhanced the thrombolysis of clots. The results are promising for increasing the specificity and positive effects of thrombolytic agents like recombinant tissue plasminogen activator (rt-PA) for the current treatment of ischemic vascular disease.
    International Journal of Pharmaceutics 06/2012; 434(1-2):384-90. DOI:10.1016/j.ijpharm.2012.06.001 · 3.65 Impact Factor
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    • "This patients repeat CT scan at 24 hours post thrombolysis demonstrated resolution of the HICAS, suggestive of clot lysis and recanalisation. This patients unusually good response to peripheral rt-PA [17] [18] [19] may have contributed a suspected type II error. Patients with a HMCAS displayed significantly more severe baseline neurological deficits than those patients without this sign. "
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    ABSTRACT: Introduction. The hyperdense internal carotid artery sign (HICAS) has been suggested as a common marker of terminal internal carotid artery (ICA) thrombus associated with poor outcomes following thrombolysis. We aimed to investigate the prevalence and prognostic significance of the HICAS in an unselected cohort of patients receiving intravenous thrombolysis. Methods. Prethrombolysis NCCTs of 120 patients were examined for the presence of the HICAS and hyperdense middle cerebral artery sign (HMCAS). A poor outcome was defined as a discharge Barthel score <15 or inpatient death. Results. A HICAS was present in 3 patients (2.5%). Prethrombolysis neurological deficits were significantly more severe in patients with a HICAS (P = 0.019). HICAS was not significantly associated with a poor outcome (P = 0.323). HMCAS was significantly associated with severe prethrombolysis neurological deficits (P = 0.0025) and a poor outcome (P = 0.015). Conclusions. This study suggests that the prevalence of the HICAS may be lower than previously reported. The presence of a HICAS was associated with severe prethrombolysis neurological deficits in keeping with terminal ICA occlusion. The role of the HICAS as a prognostic marker in stroke thrombolysis remains unclear.
    Stroke Research and Treatment 08/2011; 2011:843607. DOI:10.4061/2011/843607
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